Cutaneous TRPV1+ neurons directly sense noxious stimuli, inflammatory cytokines, and pathogen-associated molecules and are required for innate immunity against some skin pathogens. Important ...unanswered questions are whether TRPV1+ neuron activation in isolation is sufficient to initiate innate immune responses and what is the biological function for TRPV1+ neuron-initiated immune responses. We used TRPV1-Ai32 optogenetic mice and cutaneous light stimulation to activate cutaneous neurons in the absence of tissue damage or pathogen-associated products. We found that TRPV1+ neuron activation was sufficient to elicit a local type 17 immune response that augmented host defense to C. albicans and S. aureus. Moreover, local neuron activation elicited type 17 responses and augmented host defense at adjacent, unstimulated skin through a nerve reflex arc. These data show the sufficiency of TRPV1+ neuron activation for host defense and demonstrate the existence of functional anticipatory innate immunity at sites adjacent to infection that depends on antidromic neuron activation.
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•Cutaneous TRPV1+ neuron activation is sufficient to initiate type 17 inflammation•Cutaneous TRPV1+ neuron activation augments local host defense•Type 17 innate immunity via nerve reflex provides regional anticipatory immunity
Cutaneous sensory neurons can trigger an inflammatory reflex arc that activates anticipatory immunity in the neighboring skin.
Only five species account for 92% of cases of candidemia (Candida albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei); however, their distribution varies in population-based studies ...conducted in different geographical areas. C. albicans is the most frequent species, but considerable differences are found between the number of cases caused by C. glabrata and C. parapsilosis. Studies from Northern Europe and the USA reported a high number of cases caused by C. glabrata, whereas studies from Spain and Brazil demonstrated a lower number of cases caused by C. glabrata and a higher number of cases attributed to C. parapsilosis. Globally, the frequency of C. albicans is decreasing, while that of C. glabrata and C. krusei is stable, and C. parapsilosis and C. tropicalis are increasing. Patient characteristics and prior antifungal therapy also have a considerable influence on the distribution and frequency of Candida spp., regardless of the geographical area. C. albicans is more frequent in patients aged up to 18 years, the frequency of C. parapsilosis decreases with age, and C. glabrata is more common in the elderly. Finally, the presence of horizontal transmission of Candida spp. isolates (reported mainly in patients from the adult medical and post-surgical ICU, patients from oncology–haematology units, and neonates) can affect species distribution.
Candida albicans (C. albicans), a microbe commonly isolated from Candida vaginitis patients with vaginal tract infections, transforms from yeast to hyphae and produces many toxins, adhesins, and ...invasins, as well as C. albicans biofilms resistant to antifungal antibiotic treatment. Effective agents against this pathogen are urgently needed. Antimicrobial peptides (AMPs) have been used to cure inflammation and infectious diseases. In this study, we isolated whole housefly larvae insect SVWC peptide 1 (WHIS1), a novel insect single von Willebrand factor C-domain protein (SVWC) peptide from whole housefly larvae. The expression pattern of WHIS1 showed a response to the stimulation of C. albicans. In contrast to other SVWC members, which function as antiviral peptides, interferon (IFN) analogs or pathogen recognition receptors (PRRs), which are the prokaryotically expressed MdWHIS1 protein, inhibit the growth of C. albicans. Eukaryotic heterologous expression of WHIS1 inhibited C. albicans invasion into A549 and HeLa cells. The heterologous expression of WHIS1 clearly inhibited hyphal formation both extracellularly and intracellularly. Furthermore, the mechanism of WHIS1 has demonstrated that it downregulates all key hyphal formation factors (ALS1, ALS3, ALS5, ECE1, HWP1, HGC1, EFG1, and ZAP1) both extracellularly and intracellularly. These data showed that heterologously expressed WHIS1 inhibits C. albicans invasion into epithelial cells by affecting hyphal formation and adhesion factor-related gene expression. These findings provide new potential drug candidates for treating C. albicans infection.
In the human fungal pathogen Candida albicans, invasive hyphal growth is a well-recognized virulence trait. We employed transposon-mediated genome-wide mutagenesis, revealing that inactivating CTM1 ...blocks hyphal growth. CTM1 encodes a lysine (K) methyltransferase, which trimethylates cytochrome c (Cyc1) at K79. Mutants lacking CTM1 or expressing cyc1K79A grow as yeast under hyphae-inducing conditions, indicating that unmethylated Cyc1 suppresses hyphal growth. Transcriptomic analyses detected increased levels of the hyphal repressor NRG1 and decreased levels of hyphae-specific genes in ctm1Δ/Δ and cyc1K79A mutants, suggesting cyclic AMP (cAMP)-protein kinase A (PKA) signaling suppression. Co-immunoprecipitation and in vitro kinase assays demonstrated that unmethylated Cyc1 inhibits PKA kinase activity. Surprisingly, hyphae-defective ctm1Δ/Δ and cyc1K79A mutants remain virulent in mice due to accelerated proliferation. Our results unveil a critical role for cytochrome c in maintaining the virulence of C. albicans by orchestrating proliferation, growth mode, and metabolism. Importantly, this study identifies a biological function for lysine methylation on cytochrome c.
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•The methyltransferase Ctm1 is essential for the hyphal growth of Candida albicans•Ctm1 specifically catalyzes the trimethylation of cytochrome c (Cyc1) at lysine 79•Unmethylated Cyc1 binds to the catalytic subunits of PKA and inhibits their kinase activity•ctm1Δ/Δ mutant retains virulence in mice by improving proliferation via metabolic adaptation
Through a transposon-mediated genetic screen, Zeng et al. identify the methyltransferase Ctm1 as a critical regulator of hyphal growth. Ctm1 specifically methylates cytochrome c (Cyc1) at lysine 79. Unmethylated Cyc1 binds to the catalytic subunits of protein kinase A and inhibits their activity, blocking cAMP-PKA signaling and hyphal development.
The inactivation of four different microorganisms, Escherichia coli, Bacillus mycoides, Staphylococcus aureus and Candida albicans, inoculated in simulated (SWW) and real winery wastewaters (RWW), ...was assessed by the first time using free sulphate and hydroxyl radicals from photolytic (UV-A LED radiation; 370 nm) and metal Fe(II) or Co(II) activation of peroxymonosulphate (PMS). The experimental conditions tested were PMS = 0.1 mM and Fe(II) or Co(II) = 0.1 mM and pH 5.0 for the inactivation of microorganisms in SWW. However, due to the complexity of the water matrix, not unexpectedly, a fivefold concentration of reagents was required to inactivate the same organisms in RWW. In addition, compared to the bacteria, the fungus C. albicans presented a higher oxidative stress resistance to the treatments, and different experimental conditions were necessary to inactivate these cells.
After 90 min, the photolytic activation of PMS through UV-A LED radiation achieved complete inactivation of E. coli, followed by S. aureus (≈4 log) and B. mycoides (≈3 log). Total inactivation of C. albicans was also achieved, but with higher dosages of PMS (10 mM). The metal activation of PMS through the use of a transition metal Fe(II) or Co(II) accelerated the inactivation rate, particularly in the first minutes of exposure time. These treatments reached between 1 and 3 log inactivation of microorganisms in the first minute of the experiment. In addition, the use of Co(II) as promoter in the activation of PMS, was more effective in the inactivation of S. aureus and C. albicans than activation with Fe(II).
Since linear mathematical models do not adjust satisfactorily to inactivation results in all cases, different mathematical models were tested to fit the experimental inactivation data. In general, the Hom model correctly fits the inactivation results of the four microorganisms in all applied treatments. However, other models such as Biphasic and Double Weibull fit acceptably as well.
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•HSO5−/Mn+/UV-A LEDs process is highly effective in the disinfection of winery wastewater.•Total inactivation of bacteria and fungi was reached with low dosages of reagents.•Gram-positive endospore forming bacteria and fungi present the highest resistance.•Treated effluents obey Portuguese legislation for wastewater reuse in the vineyard.
Protocatechuic acid (PCA) and protocatechuic aldehyde (PAL) are important phenolic compounds in plants. We here investigated their possible beneficial effect against fungal infection and the ...underlying mechanism. The model animal of Caenorhabditis elegans was used as host, and Candida albicans was used as fungal pathogen. The nematodes were first infected with C. albicans, and the PCA and PAL treatment were then performed. Post-treatment with 10-100 μM PCA and PAL suppressed toxicity of C. albicans infection in reducing lifespan. Accompanied with this beneficial effect, treatment with 10-100 μM PCA and PAL inhibited C. albicans accumulation in intestinal lumen. In addition, treatment with 10-100 μM PCA and PAL suppressed the increase in expressions of antimicrobial genes caused by C. albicans infection. The beneficial effect of PCA and PAL against C. albicans infection depended on p38 MAPK and insulin signals. Moreover, although treatment with 10-100 μM PCA and PAL could not exhibit noticeable antifungal activity, PCA and PAL treatment obviously suppressed biofilm formation, inhibited hyphal growth, and reduced expressions of virulence genes (ALS3, CaVps34, Vma7, Vac1, and/or HWP1) related to biofilm formation and hyphal growth in C. albicans. Therefore, our data demonstrated the potential of PCA and PAL post-treatment against fungal infection and fungal virulence.
is an opportunistic yeast pathogen within the human microbiota with significant medical importance because of its pathogenic potential. The yeast produces highly resistant biofilms, which are crucial ...for maintaining infections. Though antifungals are available, their effectiveness is dwindling due to resistance. Alternate options that comprise the combination of existing azoles and polyunsaturated fatty acids, such as arachidonic acid (AA), have been shown to increase azoles susceptibility of
biofilms; however, the mechanisms are still unknown. Therefore, transcriptome analysis was conducted on biofilms exposed to sub-inhibitory concentrations of AA alone, fluconazole alone, and AA combined with fluconazole to understand the possible mechanism involved with the phenomenon.
rotein
alysis
rough
volutionary
elationships (PANTHER) analysis from the differentially expressed genes revealed that the combination of AA and fluconazole influences biological processes associated with essential processes including methionine synthesis and those involved in ATP generation, such as AMP biosynthesis, fumarate metabolism and fatty acid oxidation. These observations suggests that the interference of AA with these processes may be a possible mechanisms to induce increased antifungal susceptibility.
In this study, we describe a green and simple procedure for biosynthesis of ZnO nanoparticles using Candida albicans as eco-friendly reducing and capping agent. The synthesized ZnO nanoparticles were ...characterized by UV–vis spectroscopy, powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), photoluminescence (PL), thermo gravimetric analysis (TGA) and differential thermal analysis (DTA). The prepared nano-particles were used as catalyst for the fast and efficient synthesis of steroidal pyrazolines (4–9) from α, β-unsaturated steroidal ketones (1–3). The target molecules were obtained in good to excellent yields applying the current method.
Infections caused by the Candida species of human fungal pathogens are a significant medical problem because they can disseminate to nearly every organ of the body. In addition, there are only a few ...classes of antifungal drugs available to treat patients with invasive fungal infections. Candida infections that are associated with biofilms can withstand much higher concentrations of antifungal drugs compared with infections caused by planktonic cells, thus making biofilm infections particularly challenging to treat. Candida albicans is among the most prevalent fungal species of the human microbiota, asymptomatically colonizing several niches of the body, including the gastrointestinal tract, genitourinary tract, mouth, and skin. Immunocompromised health conditions, dysbiosis of the microbiota, or environmental changes, however, can lead to C. albicans overgrowth, causing infections that range from superficial mucosal infections to severe hematogenously disseminated infections. Here, we review the current knowledge of antifungal drug-resistance mechanisms occurring in Candida biofilms.
•Few classes of antifungal drugs currently exist to treat fungal infections.•Infections caused by Candida biofilms can be resistant to known antifungal drugs.•Growth in the biofilm state affords Candida with unique resistance mechanisms.•Antifungal drug resistance and tolerance of Candida biofilms is multifactorial.•Biofilm-resistance mechanisms involve drug-efflux pumps, the matrix, and persisters.
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